Titre du document / Document title

Drug-drug interactions of β-adrenoceptor blockers

Auteur(s) / Author(s)

BRODDE Otto-Erich ⁽¹⁾ ; KROEMER Heyo K. ⁽²⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Klinik für Nephrologie und Institut für Pathophysiologie, Klinikum der Universität Essen, Essen, ALLEMAGNE
⁽²⁾ Abteilung Allgemeine Pharmakologie, Peter Holtz Research Center of Pharmacology and Experimental Therapeutics, Klinikum der Ernst Moritz Arndt Universität, Greifswald, ALLEMAGNE

Résumé / Abstract

Patients with cardiovascular diseases are often treated by concurrent multiple drug therapy. It is therefore plausible that with an increasing number of drugs the risk of drug interactions increases. Such interactions can be either pharmacodynamic (and are due to the mechanism of the administered drugs) or they can be pharmacokinetic (resulting in a reduction or enhancement of drug elimination). Pharmacokinetic interactions can be either due to interactions at the level of drug metabolizing enzymes (most important cytochrome P450 (CYP) enzymes) or interactions at the level of drug transporter proteins (for example P-glycoprotein (MDR1)). It is important to distinguish between both mechanisms because interactions at transporter proteins can be attributed to those drugs that are not enzymatically metabolized. The scope of this article is to give an overview on clinically relevant interactions of the four β-blockers widely used in the therapy of cardiovascular diseases namely atenolol (CAS 29122-68-7), bisoprolol (CAS 66722-44-9), metoprolol (CAS 37350-58-6) (each β-1 selective), and carvedilol (CAS 72956-09-3) (β-1 and β-2 nonselective). Among these [-blockers atenolol is mainly eliminated by renal excretion, bisoprolol is in part excreted as parent compound via the renal route (50 %), the other 50% are hepatically metabolised, whereas metoprolol and carvedilol are metabolised by CYP2D6. In addition, evidence is accumulating that carvedilol is a substrate for P-glycoprotein. For these four β-blockers various pharmacodyamic and pharmacokinetic interactions have been demonstrated. Such interactions that result in an altered pharmacokinetics are mainly observed with those β-blockers that are excreted via metabolism (metoprolol and carvedilol). Accordingly these drugs have a higher potential for drug intercations. However, it should be emphasized that, in general, β-blockers are well tolerated safe drugs with a large therapeutic index.

Revue / Journal Title

Arzneimittel-Forschung   ISSN 0004-4172   CODEN ARZNAD 

Source / Source

2003, vol. 53, n^o12, pp. 814-822 [9 page(s) (article)] (1 p.3/4)

Langue / Language

Anglais

Editeur / Publisher

Cantor, Aulendorf, ALLEMAGNE  (1951) (Revue)

Mots-clés anglais / English Keywords

Elimination ; Metabolism ; Bibliographic review ; Review ; Toxicity ; Pharmacokinetic pharmacodynamic relationship ; Pharmacokinetics ; β2-Adrenergic receptor ; α1-Adrenergic receptor ; Alpha blocking agent ; β1-Adrenergic receptor ; Antagonist ; Metoprolol ; β-Adrenergic receptor ; Drug combination ; Antihypertensive agent ; Beta blocking agent ; Drug interaction ; Atenolol ; Bisoprolol ; Carvedilol ;

Mots-clés français / French Keywords

Elimination ; Métabolisme ; Revue bibliographique ; Article synthèse ; Toxicité ; Relation pharmacocinétique pharmacodynamie ; Pharmacocinétique ; Récepteur β2-adrénergique ; Récepteur α1-adrénergique ; Bloquant α-adrénergique ; Récepteur β1-adrénergique ; Antagoniste ; Métoprolol ; Récepteur β-adrénergique ; Association médicamenteuse ; Antihypertenseur ; Bloquant β-adrénergique ; Interaction médicamenteuse ; Aténolol ; Bisoprolol ; Carvédilol ;

Mots-clés espagnols / Spanish Keywords

Eliminación ; Metabolismo ; Revista bibliográfica ; Artículo síntesis ; Toxicidad ; Relación farmacocinética farmacodinamia ; Farmacocinética ; Receptor β2-adrenérgico ; Receptor α1-adrenérgico ; Bloqueador α-adrenérgico ; Receptor β1-adrenérgico ; Antagonista ; Metoprolol ; Receptor β-adrenérgico ; Asociación medicamentosa ; Antihipertensivo ; Bloqueador β-adrenérgico ; Interacción medicamentosa ; Atenolol ; Bisoprolol ; Carvedilol ;

Mots-clés d'auteur / Author Keywords

■ Atenolol ; β-Adrenoceptor blockers, drug-drug interactions ; Bisoprolol ; Carvedilol ; Metoprolol ;

Localisation / Location

INIST-CNRS, Cote INIST : 565, 35400011605608.0020